The future of regenerative medicine

The future of regenerative medicine

“Regenerative medicine is the future.”

 

We often hear this sentence as a wish that confuses what is possible with the future. Even if stem cells are already a real therapeutic opportunity today, regeneration hides the myth of a future that can exalt men’s biological power as a solution to all his evils. Researchers work tirelessly to achieve day after day, project after project, a chimerical goal: the repair of tissues and organs as a tool to heal all diseases, including aging. If we were to quantify the progress towards this ambitious goal, we would admit to not be even at 1% of this project. There are technologies, however, that are allowing medicine to make incredible leaps forward and that allows us to imagine the future, if not far at least close, of this discipline.

 

3D printing

3D printing is a technology that is gaining massive success in the most different disciplines. It is a fast, simple, and reliable method to make three-dimensional objects from a digital model through additive production, i.e. layer after layer construction. The revolution brought to the medical field is not only about tissue regeneration, but also about the possibility of modeling prostheses perfectly sized of patients. On the other hand, in regenerative medicine, 3D printing technology allows to print entire organs or to print completely autologous reparative scaffolds.

3D whole organ printing can radically change the life expectancy of patients on a transplant waiting list. In the United States, there are about 113,000 people on the waiting list and about 20 deaths every day due to the lack of a donor. 3D printing not only hides an alternative to waiting patients but offers a solution correctly modeled on their anatomy. The ink of the printer is composed of polymers and cells. The challenges in this field are different, starting from the choice of the biomaterial, which must be perfectly biocompatible and, at the same time resistant, to the complex cell geometry that makes up the tissues almost impossible to replicate artificially. This is no picnic in the case of organs such as the heart or kidney, where the challenge remains open, but in some cases, 3D printing has already been successfully used to radically change the course of a patient’s life in need. An example of a boy who received one of the first 3D printed bladder transplants is available in this TedTalk.

Also, autologous 3D printing is a novelty that aims to produce scaffolds with additive construction using as bio-ink cells and extracellular matrix elements of exclusive autologous origin, i.e. the patient himself. These are dermal matrices, but in the future, it may also be used for other tissues such as bone and cartilage, where the patient’s fat is processed to become the bio-ink. A 3D scan of the wound is made, and the extracellular matrix and the individual cells are printed accordingly. The whole procedure lasts as long as a simple surgical procedure.

 

Decellularization

It is the opposite concept of 3D printing because it benefits from subtractive rather than additive production. It opens up a great scene in the world of tissue engineering, and it revolutionizes the concept of transplantation. It involves the complete elimination of cells from a tissue or organ through methods that can be enzymatic or chemical. The final product is a supporting “skeleton” of the organ, composed exclusively of the extracellular matrix. A decellularized organ appears completely white/transparent and acts as a perfect guide for the reconstruction of the tissue that takes place through the perfusion of new cells. If it were not already evident to the readers, the advantage of replacing the cells of one organ is to allow the use of animal-derived material, which would otherwise be rejected after implantation, or by other non-compatible donors. To dive further into this subject, you could watch this video.

 

Cotton candy machines (yes, for real)

A critical aspect of transplantation is revascularization. An organ needs blood to survive, and so it must be reached by capillaries, which are structures ten times smaller in diameter than a hair. At the moment, this is an impossible challenge for 3D printing. A cotton candy machine, however, can create capillary-size polymer fibers with ease and efficiency. Once a mass of microfibers similar to the capillary network is obtained, it is covered with a perfectly biocompatible hydrogel that supports tissue regeneration. The microfibers mass immersed in the hydrogel is placed in an incubator, where a specific temperature allows the dissolution of the fibers. Only the hydrogel is left in a geometric structure that resembles the blood capillaries. If you do not want to miss the image of cotton candy in a research laboratory, click on this video.

 

Cell therapy and gene therapy

The mentioned technologies relate to organ or tissue transplantation. However, they are not sufficient when a patient suffers from a complex or systemic pathology, where the replacement of a “part” does not solve the problem. For everything else, cell and gene therapy are the most significant promises. Books should be written about this subject and not small threads, but here we only want to mention those discoveries that more than others are metaphorically the “steam engine” of medicine. As far as cell therapy is concerned, the greatest revolution has taken place thanks to the development of the so-called iPSC (induced Pluripotent Stem Cells).

We mentioned the argument in one of our articles, and it is a technology that allows obtaining pluripotent stem cells, and consequently, any other adult cell through differentiation, starting from a single somatic cell of the patient. The range of possibilities that this technology offers is almost infinite, thus becoming a widely used tool in many research laboratories, also overcoming the ethical limits of embryonic cells. Gene therapy, often called the real “future of medicine”, is a useful technology in many fields of medicine, not only regenerative. In this field, the revolution occurred thanks to the development of the CRISPR/Cas9 system, a system able to modify the genome of living beings with very high efficiency. Compared to the old gene-editing methods, CRISPR/Cas9 is precise (only the target gene is modified), fast, sustainable, and extremely versatile, able to add, replace, eliminate DNA fragments from the simplest to the most complex genomes, like ours.

It is not the aim of this article to go into the technical details of the unique technologies, but only to mention them as game-changers that have already revolutionized the sector and promise to be the absolute protagonists of the future of regenerative medicine.

Omar Sabry

 

Sources

Organ transplant waiting list statistics – US

Whole Organ 3D printing

Decellularization and cell perfusion

Cotton candy machines for regenerative medicine

iPS cells Wikipedia page

CRISPR/Cas9 Wikipedia page